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INCB001158 + daratumumab is a combination therapy under investigation for the treatment of relapsed or refractory multiple myeloma. INCB001158 (numidargistat) is a small molecule inhibitor of arginase-1, designed to modulate the immune-suppressive tumor microenvironment by increasing arginine availability and thereby potentiating T-cell mediated anti-tumor activity. Daratumumab is a human immunoglobulin G1 kappa monoclonal antibody targeting CD38, a protein highly expressed on multiple myeloma cells; it induces cell death via mechanisms including complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, and apoptosis. The combination aims to synergistically enhance anti-tumor efficacy by combining immunomodulation (via arginase inhibition) with direct antibody-mediated cytotoxicity[1][3][5].
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